资料参考

IC50 Value: 1.3nM(Ki for TS); 7.2nM(DHFR); 65nM(GARFT) Pemetrexed is approved as a first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC) with cisplatin and as a single agent for second-line treatment or for patients who show no disease progression after four cycles of platinum-based doublet induction chemotherapy as maintenance therapy. in vitro: The Ki values of the pentaglutamate of LY231514 are 1.3, 7.2, and 65 nM for inhibition against TS, DHFR, and GARFT, respectively. In contrast, although a similar high level of inhibitory potency was observed for the parent monoglutamate against DHFR (7.0 nM), the inhibition constants (Ki) for the parent monoglutamate are significantly weaker for TS (109 nM) and GARFT(9,300 nM).The parent monoglutamate LY231514 inhibited rhTS with a Ki of 109 nM when the monoglutamated form of the substrate (6R-MTHF) (6[R]-5,l0-meth ylenetetrahydrofolate) was used. This is in good agreement with the Ki value generated earlier for rmTS (Ki= 340 nM)[1]. in vivo: pemetrexed effectively reduces kidney uptake of radiofolates not only in xenografted mice but also ina syngeneic tumor mouse model[2], Clinical trial: Phase 2 study of pemetrexed and itraconazole as second-line therapy for metastatic nonsquamous non-small-cell lung cancer is reported[3]